Celia M. Marr

Current research and theories on the pathogenesis of acute laminitis in the horse.

A large number of studies have been undertaken in recent years aimed at furthering our understanding of the complex mechanisms underlying the common and debilitating condition of acute laminitis in the horse. Many of these studies have either reinforced or cast doubt on previously held theories on the pathogenesis of this disease, while others have suggested new mechanisms which may play a key role in its development. This review seeks to put the current hypotheses into the context of this recent body of evidence. While a unifying theory may not yet seem to be achievable, this review demonstrates that most of the current theories are not mutually exclusive. Studies utilising in vitro and in vivo models of the disease, particularly addressing the areas of inflammation, haemodynamic disturbances and enzyme activation in the hoof, as well as the preceding events occurring in the hindgut, have helped to explain many clinical observations of the disease and may possibly lead to more effective therapies and means of prevention in the future.

Cardiology of the Horse

Electrophysiology and Disrhythmiogenesis. Neurohumoral Control of Cardiovascular Function. Ventricular Function and the Pathophysiology of Heart Failure. Cardiac Responses to Exercies and Training. Two-Dimensional and M-Mode Echocardiography. Colour Flow Doppler Echocardiography. Transesophageal Echocardiography. Exercising Electrocardiography. Twenty-Four Hour Ambulatory Electrocardiography. Cardiac Murmurs. Dysrhythmeas. Collapse. Heart Failure. Fever: Endocarditis and Pericarditis. Cardiovascular Emergencies Under Anesthesia. Cardiovascular Disease in the Foal.

Endotoxin-induced digital vasoconstriction in horses: associated changes in plasma concentrations of vasoconstrictor mediators

REASONS FOR PERFORMING STUDY Lipopolysaccharide (LPS) infusion reduces digital perfusion, but the mediators responsible remain undetermined. OBJECTIVES To identify vasoconstrictor mediators released following LPS infusion and relate their appearance in plasma to digital blood flow alterations. METHODS Blood flow in the lateral digital vessels of 6 Thoroughbred horses, following a 30 min infusion of LPS (E. coli 055:B5; 30 ng/kg), was measured using Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures (HWST and CBST) were made. Serial blood samples were collected and plasma LPS, tumour necrosis factor alpha (TNFalpha), 5-HT, thromboxane B2 (TxB2) and endothelin measured. RESULTS Plasma LPS concentrations reached a maximum of 13.2 pg/ml during the infusion, followed by an increase in plasma TNFalpha concentration. Digital arterial and venous blood flow decreased by 43 and 63%, respectively; HWST and CBST similarly decreased. Systemic blood pressure remained unaltered. Plasma concentrations of TxB2 and 5-HT increased, coinciding with the onset of digital hypoperfusion. Plasma endothelin concentrations remained unchanged. CONCLUSIONS The temporal relationship between the onset of digital hypoperfusion and increases in plasma 5-HT and TxB2 concentrations is consistent with these platelet-derived mediators being associated with LPS-induced laminitis. POTENTIAL RELEVANCE These experimental data support the use of anti-platelet therapy in the prevention of laminitis associated with endotoxaemic conditions.

Retrospective analysis of historical, clinical, ultrasonographic, serum biochemical and haematological data in prognostic evaluation of equine liver disease

REASONS FOR PERFORMING STUDY Results of noninvasive tests of liver disease do not always correlate with the degree of hepatic disease nor outcome of the case. OBJECTIVE To investigate the prognostic value of data collected using noninvasive tests during the investigation of cases of suspected liver disease in mature horses. HYPOTHESIS Much of the data gathered during the investigation of suspected hepatopathy cases offers little prognostic guidance and interpretation of such data can be misleading. METHODS The results from a range of common and noninvasive diagnostic techniques applied in 116 mature horses with suspected liver disease, were assessed for their ability to predict survival within a 6 month period. RESULTS A significantly poorer prognosis was found in association with clinical signs suggestive of liver disease, presence of hepatic encephalopathy, ultrasonographic abnormalities, increased serum globulins, increased total bile acids (TBA), increased alkaline phosphatase (AP), increased gamma-glutamyl transferase (gammaGT), erythrocytosis, leucocytosis, low serum albumin and low serum urea. Additional significant novel findings of interest included an association between increased plasma fibrinogen and low serum creatinine concentrations with nonsurvival in cases of liver disease, an association between raised serum concentrations of AP and gammaGT with biliary hyperplasia and also an association between hepatic fibrosis, haemosiderosis and biliary hyperplasia with ultrasonographically detected hepatic abnormalities. CONCLUSIONS The most useful noninvasive prognostic test in cases of suspected liver disease in mature horses is the severity of clinical signs. Other data may be of some limited prognostic value. POTENTIAL RELEVANCE Application of the findings in this study may not be directly applicable to other case populations. However, the findings should at least be considered when prognosis is based on similar criteria.

The effects of vasoactive amines found in the equine hindgut on digital blood flow in the normal horse

REASONS FOR PERFORMING STUDY Disturbances of digital blood flow are thought to be fundamental to the pathophysiology of acute laminitis. However, factors linking the initiating events in the equine hindgut with these disturbances in the foot remain to be determined. HYPOTHESIS Amine compounds, formed by bacteria in the equine hindgut, have digital vasoconstrictor effects in vivo. METHODS Tryptamine (1.6 microg/kg/min) and phenylethylamine (2.13 microg/kg/min) were infused i.v. into standing nonsedated horses. Digital blood flow was measured by Doppler ultrasound and foot surface temperature was monitored. Plasma 5-hydroxytryptamine (5-HT) concentrations were measured by HPLC. RESULTS Tryptamine and phenylethylamine infusions had no effect on systemic arterial blood pressure or heart rate, but caused significant decreases in digital arterial blood flow (mean +/- s.e. 29.2 +/- 8.5 and 18.4 +/- 6.8%, respectively). Both amines also caused decreases in dorsal hoof wall temperature (0.6 +/- 0.1 and 0.5 +/- 0.1 degrees C for tryptamine and phenylethylamine, respectively) and concomitant increases in plasma 5-HT concentration. CONCLUSIONS Tryptamine and phenylethylamine caused reduction of digital blood flow, effects which may have been mediated, in part, via displacement of 5-HT from platelets. POTENTIAL RELEVANCE Amine compounds occurring in the equine hindgut, if released into the circulation following carbohydrate overload, could contribute to selective digital vasoconstriction. Further work in ponies and horses, with naturally occurring laminitis, is necessary to determine whether amines represent a therapeutic target in this disease.

Epidemiological study of pasture-associated laminitis and concurrent risk factors in the South of England

A retrospective study of laminitis was carried out to identify risk factors associated with this disease on an East Anglian farm with approximately 1000 animals living in an area of 1000 acres. Medical records between January 1997 and May 2000 and between April 2005 and March 2008 were reviewed, and the age, sex, weight (kg), height (inches [in] and hands [H]) and weight-to-height ratio (kg/in) was recorded. The prevalence, incidence and seasonality of laminitis were determined and their relationship to the monthly temperature, rainfall and hours of sunshine was evaluated. Averaged over the six years, the highest prevalence (2.6 per cent) and incidence (16 cases/1000 animals) of laminitis occurred in May. The findings of a multivariate analysis revealed that females (P=0.007, odds ratio [OR] 1.46, 95 per cent confidence interval [CI] 1.1053 to 1.9646) and light animals (P≤0.001, OR=0.995, 95 per cent CI =0.9932 to 0.9963) had the greatest risk of developing laminitis. A positive association was found between hours of sunshine and incidence (P=0.007, relative risk [RR] 1.009, 95 per cent CI 1.001 to 1.012) and prevalence (P=0.002, RR 1.008, 95 per cent CI 1.003 to 1.012) of laminitis. The data suggest that there is a relationship between season, sex of the animal and the development of laminitis.

Development and application of a scoring system for prognostic evaluation of equine liver biopsies

REASONS FOR PERFORMING STUDY The study was designed to investigate the prognostic value of liver biopsy during investigation of cases of suspected liver disease in mature horses. HYPOTHESIS That liver biopsy is the most prognostically useful technique in common usage in the investigation of suspected liver disease. METHODS This study examined the prognostic value of liver biopsy during the investigation of suspected liver disease in 73 mature horses. Histopathological variables comprising fibrosis, irreversible cytopathology, inflammatory infiltration, haemosiderin accumulation and biliary hyperplasia were found to be significant predictors of nonsurvival and were used to formulate a weighted biopsy score representing a prognostically useful broad comparative index of histopathological severity. Minimum and maximum possible scores were 0 and 14 points, respectively. RESULTS Retrospective application of the biopsy scoring system to the study population indicated that horses with scores of 0 or 1 were equally likely to survive to 6 months with a combined mortality of 4%. Horses with biopsy scores between 2 and 6 had a combined mortality of 33% and were at a 12-fold increased risk of nonsurvival within 6 months (hazard ratio = 12.04, 95% CI 134-107.81, P = 0.026) compared to horses with a biopsy score of 0. Horses with biopsy scores between 7 and 14 had a combined mortality of 86% and were at a 46-fold increased risk of nonsurvival (hazard ratio = 46.01, 95% CI 5.92-357.5, P < 0.001) compared to horses with biopsy score 0. CONCLUSIONS Application of the biopsy scoring system to histopathological findings in liver biopsy specimens was very useful in predicting survival of cases of suspected liver disease. POTENTIAL RELEVANCE Application of the findings in this study may not be directly applicable to other case populations. However, liver biopsy appears to be the most valuable prognostic technique employed during the investigation of suspected cases of liver disease in mature horses.

Identification and quantification of amines in the equine caecum

Acute laminitis has been associated with the release of compounds, as yet unidentified, produced by hindgut fermentation which affect blood flow to the digit. The objectives of this study were to identify amine compounds in equine caecal and colonic contents, some of which are known to have vasoactive properties. In addition, the concentrations of amines in caecal contents of horses fed either grass or hay diets were compared. Fifteen amines were identified in equine hindgut contents in concentrations greater than 1 microM. The caecal concentrations of phenylethylamine, isoamylamine, cadaverine, diaminoheptane and spermidine were significantly higher in horses on spring/summer grass compared with those on winter grass or hay. These data show that many amines are present in the equine hindgut, some of which may have the potential to cause peripheral vasoconstriction if released into the circulation from the gastrointestinal tract.

Demonstration of regional differences in equine ventricular myocardial velocity in normal 2-year-old thoroughbreds with Doppler tissue imaging

REASONS FOR PERFORMING STUDY Doppler tissue imaging (DTI) is a novel noninvasive method by which myocardial velocity can be assessed directly and it allows regional, rather than global, cardiac function to be evaluated. HYPOTHESIS That regional differences in myocardial velocities exist within the equine ventricle. OBJECTIVES To develop a repeatable examination technique for DTI in horses, describe DTI findings in various regions of the normal equine ventricle, compare colour (CDTI) and spectral (SDTI) techniques of DTI, and document regional differences in myocardial velocity. METHODS Five regions of the ventricles (right ventricular wall, interventricular septum and left, right and caudal regions of the left ventricle) were evaluated using SDTI and CDTI in 20 clinically normal Thoroughbreds age 2 years. Individual repeatability of the method was determined by examination of one 6-year-old Thoroughbred on 6 occasions. RESULTS Three major movements were observed in the ventricular walls in systole, early diastole and late diastole. The interventricular septum had a complex pattern of movement. The left region of the left ventricle and interventricular septum had the most rapid movement. The individual repeatability of CDTI was poor, while in systole and early diastole, but not late diastole, SDTI produced repeatable estimates of maximal myocardial velocity. The different velocity estimates obtained with SDTI and CDTI are not interchangeable. Regional differences in the peak mean and maximal myocardial velocities were found in systole and early diastole (P<0.05), but were not identified in late diastole. CONCLUSIONS The SDTI modality appears to produce the most repeatable data. There are regional differences in myocardial velocity within the equine ventricles for systole and early diastole. POTENTIAL RELEVANCE DTI shows potential as a tool for studying regional myocardial movement both in clinical cases suspected of having myocardial dysfunction and in a research setting. In particular, SDTI offers potential as a direct and noninvasive means to study early diastolic function of the equine ventricles.

Equine hepatic disease: the effect of patient- and case-specific variables on risk and prognosis

REASONS FOR PERFORMING STUDY Liver disease is fairly common in horses and, although previous literature suggests that fatality rates are high, impressions gained from current clinical practice suggest that this is no longer the case. OBJECTIVES A case-control study was undertaken in 2 hospitals to investigate whether age, gender or breed type predisposed horses to developing hepatic disease, with the additional aim of determining whether these factors and disease category had any effect on outcome. METHODS Eighty-eight cases were identified by review of computerised archives at 2 hospitals. Three cases admitted immediately before and after the cases were used as controls. Multivariant models were developed to explore the relationship between age, breed type and gender and the development of liver disease, and within the clinical cases, to identify whether any of these factors or specific forms of liver disease were associated with fatality rate. RESULTS Ponies were more likely to develop hepatic disease than light riding horses, but neither age nor gender were significant risk factors. Overall, the fatality rate was fairly low; horses with unclassified hepatopathies had the lowest fatality rate and those with cholangiohepatitis, pyrrolizidine alkaloid toxicity and chronic active hepatitis had significantly higher fatality rates in comparison. However, age, breed type and gender had no detectable effect on outcome. CONCLUSIONS AND POTENTIAL RELEVANCE Such data could be of particular value to equine practitioners, as the cases were drawn from both primary and referral practice, and were all seen within the last 5 years.